Abstract

Background:

The failure of all clinical trials to treat Alzheimer’s disease (AD) indicates that the current approach of modifying disease is either wrong or is too late to be efficient. Mild cognitive impairment (MCI) denotes the phase between the preclinical phase and clinical overt dementia. AD mouse models that overexpress human amyloid-β (Aβ) are used to study disease pathogenesis and to conduct drug development/testing. However, there is no direct correlation between the Aβ deposition, the age of onset and the severity of cognitive dysfunction.

Objective:

To detect and predict MCI when Aβ plaques start to appear in the hippocampus of an AD mouse.

Methods:

We trained wild-type and AD mice in a Morris water maze (WM) task with different inter-trial intervals (ITI) at 3 months of age and assessed their WM performance. Additionally, we used a classification algorithm to predict the genotype (APPtg versus wild-type) of individual mice from their respective WM data.

Results:

MCI can be empirically detected using a short-ITI protocol. We show that the ITI modulates the spatial learning of AD mice without affecting the formation of spatial memory. Finally, a simple classification algorithm such as logistic regression on WM data can give an accurate prediction of the cognitive dysfunction of a specific mouse.

Conclusion:

MCI can be detected as well predicted simultaneously with the onset of Aβ deposition in the hippocampus in AD mouse model. The mild cognitive impairment prediction can be used for assessing the efficacy of a treatment.

中文翻译：

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阿尔茨海默病小鼠轻度认知障碍的检测和预测。

摘要

背景：

治疗阿尔茨海默病 (AD) 的所有临床试验均失败表明，目前改变疾病的方法要么是错误的，要么为时已晚，无法有效。轻度认知障碍 (MCI) 表示临床前阶段和临床明显痴呆之间的阶段。过度表达人类淀粉样蛋白-β (Aβ) 的 AD 小鼠模型用于研究疾病发病机制并进行药物开发/测试。然而，Aβ沉积、发病年龄和认知功能障碍的严重程度之间没有直接相关性。

客观的：

当 Aβ 斑块开始出现在 AD 小鼠的海马中时，检测和预测 MCI。

方法：

我们在 3 个月大时以不同的试验间间隔 (ITI) 在莫里斯水迷宫 (WM) 任务中训练野生型和 AD 小鼠，并评估它们的 WM 表现。此外，我们使用分类算法根据各自的 WM 数据预测单个小鼠的基因型（APPtg 与野生型）。

结果：

MCI 可以使用短 ITI 协议凭经验检测。我们表明 ITI 调节 AD 小鼠的空间学习而不影响空间记忆的形成。最后，一个简单的分类算法，如对 WM 数据的逻辑回归，可以准确预测特定小鼠的认知功能障碍。

结论：

在 AD 小鼠模型海马中 Aβ 沉积开始的同时，也可以检测到 MCI。轻度认知障碍预测可用于评估治疗效果。